Qualitative analysis of pharmacogenetic applications in pediatric clinical trials registered on ClinicalTrials.gov

Pharmacogenetics (PGx) may support more individualized pediatric therapy by accounting for genetic variability in drug response, toxicity, and dose requirements. However, the extent and manner in which pharmacogenetic and biomarker-related components are incorporated into pediatric clinical trials remain incompletely characterized.

To qualitatively examine how pharmacogenetic and biomarker-related components are represented and operationalized in pediatric clinical trials registered on ClinicalTrials.gov, with emphasis on disease distribution, apparent roles within trial design, and the primary and secondary outcome domains reported in these studies.

A registry-based qualitative analysis was conducted using ClinicalTrials.gov. Interventional Phase II to IV trials enrolling participants younger than 18 years of age were screened from database inception through July 2025 using pharmacogenetic-related search terms. Eligible studies included pediatric trials incorporating pharmacogenetic or pharmacogenomic components relevant to drug response, efficacy, toxicity, pharmacokinetics/pharmacodynamics, dose optimization, or treatment selection. Included trials were classified by primary clinical disease category, apparent level of pharmacogenetic integration, and primary and secondary outcome domains.

A total of 198 pediatric trials met the inclusion criteria. Infectious diseases and oncology were the most frequently represented primary clinical disease categories, each accounting for 37 (18.7%) of included trials, followed by psychiatry and respiratory diseases at 20 (10.1%) each. Exploratory or observational incorporation of pharmacogenetic or biomarker-related information was the most common pattern, accounting for 121 (61.1%) of trials, whereas guided intervention and decision-informing use accounted for 39 (19.7%) and 25 (12.6%), respectively. At the primary outcome level, clinical efficacy was the dominant domain, accounting for 82 (41.4%) of trials, followed by biomarkers/molecular outcomes at 48 (24.2%). Among secondary outcomes coded as inclusive occurrences, biomarkers/molecular outcomes were the leading category at 116 (27.0%), followed by clinical efficacy at 103 (24.0%).

Pediatric pharmacogenetic trials appear to be advancing but remain largely positioned at an intermediate translational stage. Pharmacogenetic and biomarker-related components were more often exploratory than treatment-guiding, highlighting the need for clearer registry reporting and more explicit trial designs that distinguish exploratory, decision-informing, and clinically actionable PGx roles.